Page 42 - Read Online

Politei et al. Rare Dis Orphan Drugs J 2024;3:10 https://dx.doi.org/10.20517/rdodj.2023.46 Page 9 of 12

these components. The implementation of the low-FODMAP diet led to significant improvements in
indigestion, diarrhea, and constipation. The authors concluded that a low-FODMAP diet could serve as an
[52]
effective alternative approach to enhance intestinal manifestations and overall quality of life . These
changes in food consumption also allowed patients to adapt the intake of the foods most related to the
clinical GI signs (gluten, lactose, and some vegetables).

Lenders et al. shared their experience with seven Fabry patients who utilized commercially available oral
dietary supplements, providing a daily dose of 1800 U AGAL over a period of 90 to 180 days . Overall, the
[54]
intensity of abdominal pain notably decreased after 8 weeks and continued to do so after 12 weeks. The
frequency of diarrhea also showed a slight decrease from 2.6 days per week to 0.5 days per week.
Importantly, none of the patients experienced heightened GI symptoms during the observation period, with
[54]
all reporting a general improvement in GI symptoms and an enhanced sense of well-being .
Monticelli et al. reported a co-chaperone role for curcumin in addition to AGAL pharmacological
chaperones (1-deoxygalactonojirimycin-DGJ- and galactose) in a cell model . The associated therapy with
[54]
curcumin and pharmacological chaperones proved beneficial for 4 out of 5 tested mutants and showed fold
increases ranging from 1.1 to 2.3 for DGJ and from 1.1 to 2.8 for galactose. In the case of one mutant
(L300F), long-term treatment revealed an enhancement in GL-3 clearance and lysosomal markers . In a
[55]
study exploring early adjunctive antioxidant treatment to mitigate oxidative stress markers, 10 Fabry
[56]
patients were subjected to adjuvant treatment with green tea . Oxidative stress markers p22 and
phox
MYPT-1 phosphorylation decreased after ERT and significantly further decreased after green tea
administration. While ERK 1/2 phosphorylation and MDA levels remained unchanged after ERT, they
experienced a significant decrease after green tea. Additionally, Heme oxygenase-1 exhibited a significant
increase after ERT, which was further augmented following green tea treatment. These findings underscore
an antioxidative effect exerted by ERT, further magnified by the adjunctive antioxidant treatment with
[56]
green tea .
CONCLUSIONS
The recognition of GI manifestations in Fabry disease allows to suspect this condition and achieve a
diagnosis in the early stages of the disease, and these symptoms can also justify the initiation of specific
treatment in patients with a classic phenotype.

Although published management guidelines suggest studies to evaluate the severity of GI involvement and
the prescription of non-specific symptomatic treatments, there is still an unmet need for the design of a
consensus that describes in detail which clinical evaluations should be used for routine monitoring, and
what adjuvant therapies and dietary plans are most effective in controlling symptoms. Future perspectives in
relation to new lines of research seek to elucidate the interactions of the brain-gut axis, as well as the role
that the intestinal microbiota plays in pathophysiology.

DECLARATIONS
Author contributions
Conceptualization, writing, revision, conceptualization and validation: Politei JM, Solar B
Writing: Politei JM
Validation: Politei JM
Both authors have read and agreed to the published version of the manuscript.